Rural treatment of acute cardiogenic pulmonary edema: applying the evidence to achieve success with failure.

Rural management of acute cardiogenic pulmonary edema should be based on avoidance of adverse outcomes such as in-hospital mortality, the need for intensive care unit care, and the need for intubation and mechanical ventilation. Current evidence suggests that early noninvasive continuous positive airway pressure and early aggressive preload reduction with intravenous nitroglycerin are first-line interventions. Afterload reduction with sublingual captopril, with or without nitroglycerin, improves outcomes and is a second-line intervention. Furosemide is associated with adverse outcomes when used alone and should be given only after vasodilator therapy as a third-line intervention. Inotropes should be used only with demonstrably poor perfusion as they do not improve outcomes and may indeed be associated with increased mortality. Concurrent vasodilator therapy should be considered as soon as possible. Morphine should not be used as it is associated with adverse outcomes. If sedation is desirable, benzodiazepines should be considered.

[Comparative efficacy of fixed dose combinations of enalapril with hydrochlorothiazide and captopril with hydrochlorothiazide in patients with high risk hypertension].

Clinical effectiveness and tolerability of o.d. use of fixed dose combinations of enalapril (10 mg) with hydrochlorothiazide (25 mg) (Enap H) and captopril (50 mg) with hydrochlorothiazide (25 mg) (Capozide) were compared in a randomized study on 60 patients with I-II degree high and very high risk hypertension. Study duration was 6 months, number of patients in each of parallel groups -- 30. Antihypertensive activity, ability to improve arterial elasticity and T/P parameter, cost/efficacy index of enalapril (10 mg) plus hydrochlorothiazide (25 mg) combination was found to be superior to those of captopril (50 mg) plus hydrochlorothiazide (25 mg) combination.

Resource use, costs, and quality of life among patients in the multinational Valsartan in Acute Myocardial Infarction Trial (VALIANT).

BACKGROUND: In a multinational clinical trial, valsartan was statistically not inferior to captopril in reducing mortality and cardiovascular morbidity after myocardial infarction (MI) in patients with signs of heart failure and/or left ventricular dysfunction. We conducted a prospective economic evaluation to compare within-trial resource use, costs, and quality of life in patients receiving valsartan, captopril, or both after MI. METHODS: We assigned country-specific unit costs to resource use data for 14703 patients and measured health-related quality of life in a subset of 4524 patients. We used the nonparametric bootstrap method to compare rates of resource use and costs, and a piecewise linear mixed-effects regression analysis to compare longitudinal measures of quality of life. RESULTS: There were no significant differences in rates of resource use between the valsartan and captopril groups. During an average follow-up of 2 years, total costs for patients receiving valsartan were significantly higher than for patients receiving captopril (USD 14103 vs USD 13038; 95% CI USD 369-USD 1875). The cost differential was caused primarily by the cost of the study medications (USD 1056 for valsartan vs USD 165 for captopril; 95% CI USD 867 to USD 912). Quality of life did not differ significantly between groups. CONCLUSIONS: For most patients at high risk after MI, the availability of generic captopril confers a cost advantage over valsartan because of lower medication costs. The difference will be smaller or nonexistent in settings where brand-name ACE inhibitors are prescribed.

Cost effectiveness of ACE inhibitor treatment for patients with type 1 diabetes mellitus.

OBJECTIVE: Current guidelines recommend treating patients with type 1 diabetes mellitus with ACE inhibitors after the onset of microalbuminuria. Recent clinical trials have shown ACE inhibitors can affect the development of nephropathy when initiated prior to the onset of microalbuminuria. Our objective is to examine the cost effectiveness of treating adults aged over 20 years with an ACE inhibitor (captopril) immediately following diagnosis of type 1 diabetes versus treating them after the onset of microalbuminuria. DESIGN: Using a semi-Markov model, we calculated four main outcome measures: lifetime direct medical costs (discounted), QALYs, cumulative incidence of end-stage renal disease (ESRD), and number of days of ESRD over a lifetime. Medical costs are in 1999 US dollars. SETTING: All analyses were from the viewpoint of a single US payer responsible for all direct medical costs, including screening for microalbuminuria, ACE inhibitor treatment (captopril), management of major diabetic complications, and routine annual medical costs not specific to diabetes. METHODS: We applied the model to a hypothetical cohort of 10,000 persons newly diagnosed with type 1 diabetes. Distribution of sex and race/ethnicity within the cohort is representative of the general US population. RESULTS: We estimated that the incremental cost of early use of captopril for the average adult with type 1 diabetes is USD 27,143 per QALY. This level varies considerably with age and glycaemic level. When the age at onset of diabetes is 20 years and glycosylated haemoglobin (HbA(1c)) level is 9%, the cost-effectiveness ratio is USD 13,814 per QALY. When the age at onset is 25 years and HbA(1c) level is 7%, the cost-effectiveness ratio is USD 39,530 per QALY. CONCLUSION: This model, with its underlying assumptions and data, suggests that early treatment with captopril provides modest benefit at reasonable cost effectiveness, from the US single-payer perspective, in the prevention of ESRD compared with delaying treatment until diagnosis of microalbuminuria. Early treatment with other ACE inhibitors will provide similar cost effectiveness if they have equivalent efficacy, compliance and price per dose. Treatment may be considered among patients at age 20 years with new onset of type 1 diabetes. This conclusion is sensitive to the extent that ACE inhibitors delay onset of microalbuminuria. Other factors such as the patient's age and glycaemic level must be considered when deciding to initiate early treatment.

HOPE study impact on ACE inhibitors use.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are used to treat cardiovascular diseases, major causes of death in Canada. The HOPE (Heart Outcomes Prevention Evaluation) study showed that ramipril benefits patients at high risk for cardiovascular disease. We analyzed ACE inhibitor use and costs in Canada before and after publication of HOPE. METHODS: We obtained pharmacy and hospital sales data for 1985-2001 from IMS Canada for all ACE inhibitors (Anatomical Therapeutic Category code C09A0) and for the 3 largest provinces (i.e., British Columbia, Quebec, Ontario). Prescription numbers, total costs, cost/prescription, and market share of individual ACE inhibitors were plotted over time and analyzed using regression. Canadian dollars were used to report costs. RESULTS: We examined 10 drugs; captopril was the first, introduced in 1985. Overall, prescriptions increased consistently from 356 000 in 1985 to 11.5 million in 2001, representing an annual increase of 660 000 (y = 661 410x-510 360; r(2) = 0.99). Total costs increased linearly from 1985 (14.5 million US dollars) to 2001 (513 million US dollars): Y = 29.3.10(6)x - 29.9.10(6); r(2) = 0.99. Provincial utilization patterns were also similar. Ramipril's national use increased dramatically from 1999 (822 000 prescriptions, 9.2% of all ACE inhibitors) to 2001 (3.8 million, 32.8% of all ACE inhibitors). National costs for ramipril increased exponentially (y = 1.08e(0.6248x)) to a total of 157 million US dollars in 2001, with the 3 major provinces accounting for 78.9%. Costs per prescription followed no observable trend (range 39.45-46.20 US dollars). CONCLUSIONS: The number of prescriptions and the total cost of ACE inhibitors increased over the period studied. Ramipril use increased in concert with publication of the HOPE trial, while the growth rates of other ACE inhibitors remained constant.

An economic evaluation of atenolol vs. captopril in patients with Type 2 diabetes (UKPDS 54).

AIMS: To compare the net cost of a tight blood pressure control policy with an angiotensin converting enzyme inhibitor (captopril) or beta blocker (atenolol) in patients with Type 2 diabetes. DESIGN: A cost-effectiveness analysis based on outcomes and resources used in a randomized controlled trial and assumptions regarding the use of these therapies in a general practice setting. SETTING: Twenty United Kingdom Prospective Diabetes Study Hospital-based clinics in England, Scotland and Northern Ireland. SUBJECTS: Hypertensive patients (n = 758) with Type 2 diabetes (mean age 56 years, mean blood pressure 159/94 mmHg), 400 of whom were allocated to the angiotensin converting enzyme inhibitor captopril and 358 to the beta blocker atenolol. MAIN OUTCOME MEASURES: Life expectancy and mean cost per patient. RESULTS: There was no statistically significant difference in life expectancy between groups. The cost per patient over the trial period was 6485 UK pounds in the captopril group, compared with 5550 UK pounds in the atenolol group, an average cost difference of 935 UK pounds (95% confidence interval 188 UK pounds, 1682 UK pounds). This 14% reduction arose partly because of lower drug prices, and also because of significantly fewer and shorter hospitalizations in the atenolol group, and despite higher antidiabetic drug costs in the atenolol group. CONCLUSIONS: Treatment of hypertensive patients with Type 2 diabetes using atenolol or captopril was equally effective. However, total costs were significantly lower in the atenolol group. Diabet. Med. 18, 438-444 (2001)

Genéricos y precios de referencia, rangode precios y fuentes de información / Generic medicines and Reference Pricing System, price rating and information

El consumo de las Especialidades Farmacéuticas Genéricas (EFG) en España en el Sistema Nacional de Salud no se puede precisar, ya que no existen datos fiables publicados de los mismos, solo declaraciones y notas de prensa. Se podría decir que el consumo de EFG en España, estimado en un 2 por ciento de la facturación del Sistema Nacional de Salud en 2000, ha crecido pero es todavía demasiado bajo comparado con el consumo en la Unión Europea y EE.UU. Se estudia un grupo de seis principios activos (10 por ciento de los existentes) en forma de EFG, seleccionados entre los principios activos mas consumidos en envases en 1999 en el Sistema Nacional de Salud. La información obtenida en fuentes de información accesibles, sobre las EFG registradas y comercializadas en España de este grupo, no es coincidente y es difícil de obtener. De este grupo, una selección aleatoria de formatos que tienen un conjunto homogéneo (alprazolam comprimidos, amoxicilina sobres, captopril comprimidos, diclofenaco supositorios, omeprazol cápsulas y ranitidina comprimidos), presenta una variabilidad de precios expresado en coste de una Dosis Diaria Definida que puede llegar a ser hasta tres veces mayor el más alto que el más bajo (rango 1,2 - 3 veces).En seis conjuntos homogéneos seleccionados aleatoriamente entre los anteriores, existe un rango amplio de los precios (24 por ciento - 89 por ciento, precio más bajo con relación al precio de referencia), lo que indica que no se aplica estrictamente las reglas del mercado (precio de referencia el más barato). El Proceso de puesta en marcha de los precios de referencia ha sido largo; el número de conjuntos homogéneos ha sido menor que las posibilidades existentes; y el sistema de establecimiento del precio de referencia ha sido restrictivo (precio de referencia no es el más barato) (AU)

Perindopril + indapamide: new preparation. Simple trick.

(1) The combination of perindopril 4 mg + indapamide 1.25 mg is approved for second-line treatment of hypertension after failure of perindopril alone. (2) The other combination, of a low dose of an angiotensin-converting-enzyme inhibitor (2 mg of perindopril) and a diuretic (0.625 mg of indapamide), is being promoted as first-line treatment of hypertension. (3) The clinical files for both preparations are limited to the strict minimum. (4) A dose-finding study showed that the perindopril 4 mg + indapamide 1.25 mg dose combination offered the best risk-benefit ratio by comparison with combinations containing the same perindopril dose but other indapamide doses. (5) A double-blind trial suggests that the antihypertensive activity of the perindopril 4 mg + indapamide 1.25 mg combination is equivalent to that of the captopril 50 mg + hydrochlorothiazide 25 mg and enalapril 20 mg + hydrochlorothiazide 12.5 mg combinations. The safety profile was the same for the three combinations. (6) The 2-mg perindopril combination has not been compared with perindopril monotherapy at the usual dose of 4 mg, or with indapamide monotherapy at a mean dose of 2.5 mg. (7) The two combinations are costlier than their competitors.

Cost effectiveness analysis of improved blood pressure control in hypertensive patients with type 2 diabetes: UKPDS 40. UK Prospective Diabetes Study Group.

OBJECTIVES: To estimate the economic efficiency of tight blood pressure control, with angiotensin converting enzyme inhibitors or beta blockers, compared with less tight control in hypertensive patients with type 2 diabetes. DESIGN: Cost effectiveness analysis incorporating within trial analysis and estimation of impact on life expectancy through use of the within trial hazards of reaching a defined clinical end point. Use of resources driven by trial protocol and use of resources in standard clinical practice were both considered. SETTING: 20 hospital based clinics in England, Scotland, and Northern Ireland. SUBJECTS: 1148 hypertensive patients with type 2 diabetes from UK prospective diabetes study randomised to tight control of blood pressure (n=758) or less tight control (n=390). MAIN OUTCOME MEASURE: Cost effectiveness ratios based on (a) use of healthcare resources associated with tight control and less tight control and treatment of complications and (b) within trial time free from diabetes related end points, and life years gained. RESULTS: Based on use of resources driven by trial protocol, the incremental cost effectiveness of tight control compared with less tight control was cost saving. Based on use of resources in standard clinical practice, incremental cost per extra year free from end points amounted to pound1049 (costs and effects discounted at 6% per year) and pound434 (costs discounted at 6% per year and effects not discounted). The incremental cost per life year gained was pound720 (costs and effects discounted at 6% per year) and pound291 (costs discounted at 6% per year and effects not discounted). CONCLUSIONS: Tight control of blood pressure in hypertensive patients with type 2 diabetes substantially reduced the cost of complications, increased the interval without complications and survival, and had a cost effectiveness ratio that compares favourably with many accepted healthcare programmes.

Pharmacoeconomics of angiotensin converting enzyme inhibitors in heart failure.

As a result of the increasing cost of health care and the limited resources available, it has become more difficult to allocate resources efficiently and effectively in the health care system. This environment has led to the development of pharmacoeconomic studies, which have been designed in response to the need for assessment of the economic benefits of a product prior to its acceptance in the market. The field of pharmacoeconomics has grown rapidly, especially in relation to the development of new pharmacological products. Economic analysis is now routinely incorporated into many clinical trials, and this type of information, in conjunction with the usual safety and efficacy data, is becoming more important to pharmaceutical companies, regulatory authorities, third party payers, and end-users. The cost-effectiveness of angiotensin converting enzyme (ACE) inhibitors for the treatment of heart failure has been evaluated on the basis of a number of large-scale studies, including the Survival and Ventricular Enlargement (SAVE) study and the Veterans Administration Cooperative Vasodilator Heart Failure Trials (V-HeFT I and II). The cost-effectiveness of the ACE inhibitor captopril compares favorably with other cardiac interventions, reducing both mortality and the incidence of congestive heart failure (CHF). Captopril also appears to be cost-effective in the treatment of patients with left ventricular dysfunction after acute myocardial infarction. In addition, analysis of more recent studies of the treatment of fosinopril in patients with mild to moderate CHF have been performed and have proved this newer ACE inhibitor to be cost-saving in these patients.

Economic evaluation of ACE inhibitor treatment of nephropathy in patients with insulin-dependent diabetes mellitus in Italy.

Diabetic nephropathy is one of the major complications of insulin-dependent diabetes mellitus (IDDM), with proteinuria being the main clinical manifestation of diabetic nephropathy. Most patients who develop overt proteinuria progress to end-stage renal disease (ESRD), usually within 5 to 7 years; ESRD necessitates dialysis or renal transplantation. Although a relationship between blood pressure reduction and delaying of ESRD has been assumed for a long time, only recently has a controlled randomised clinical trial shown that the treatment of diabetic nephropathy with an ACE inhibitor can significantly delay the loss of renal function and, therefore, ESRD. Consistent with the clinical trial on which this economic evaluation was based, the costs and consequences of 2 alternatives were considered: (i) patients subject to blood pressure control with only antihypertensive medication, but without an ACE inhibitor (placebo group) and (ii) patients given ACE inhibitor therapy (captopril group) with similar blood pressure control to the placebo group. This cost-effectiveness analysis was performed from the perspective of the Italian National Health Service [Servizio Sanitario Nazionale (SSN)]. Accordingly, only direct costs related to publicly funded healthcare services were included. The number of dialysis-years avoided (DYA) was the clinical end-point. A 10-year time horizon was considered for the economic evaluation. Captopril therapy was dominant, being at the same time more effective and less costly. The total cost for the captopril alternative during the 10-year period was 21,901,625 Italian lire (L; 1993 values) per patient, while total cost for the placebo alternative was L30,352,590 per patient. Compared with placebo, 20.01 DYA per 100 patients treated were estimated with captopril therapy during the trial period, equivalent to 2.4 months per patient. The robustness of this result was confirmed by sensitivity analysis: for both extremes, captopril remained dominant. This economic evaluation, requested by the Italian Ministry of Health, demonstrated savings in healthcare expenditure with the use of an ACE inhibitor in patients with proteinuria.

Modelling and costing the consequences of using an ACE inhibitor to slow the progression of renal failure in type I diabetic patients.

Antihypertensive drugs slow the progressive decline in renal function seen in patients with insulin-dependent diabetes and nephropathy. In a recent study, the ACE inhibitor captopril protected against this deterioration in renal function. We developed an economic model to analyse the cost impact of ACE inhibitor treatment on progression to endstage renal failure (ESRF) in diabetic patients over 4 years. Two scenarios were compared: one describing the progression of a cohort of 1000 patients receiving 25 mg captopril three times daily, and the other for an equivalent cohort without such prophylactic treatment. Previously published data were used to estimate the transition rates for each stage from the onset of renal failure until death. All direct costs were discounted by an annual rate of 6%, and were subjected to sensitivity analysis. The discounted cost saving of ACE inhibitor treatment for a cohort of 1000 patients was estimated as 0.95 million pounds over 4 years. Under sensitivity analysis, these results were very robust to variations in the costs of ESRF treatment. Prophylactic treatment with ACE inhibitors was predicted to provide substantial increases in life expectancy and reduction in the incidence of ESRF, while also providing significant economic savings.

An economic analysis of captopril in the treatment of diabetic nephropathy. The Collaborative Study Group.

OBJECTIVE: The results of a recent clinical trial. The Effect of ACE inhibition on Diabetic Nephropathy, demonstrated that captopril reduced the rate of renal failure, end-stage renal disease (ESRD), and death in patients with IDDM and nephropathy. The purpose of this study was to determine the cost-benefit and cost-effectiveness of captopril as a therapy in patients with IDDM as well as the potential savings for all patients with diabetes and nephropathy. RESEARCH DESIGN AND METHODS: We used the results from a randomized, placebo-controlled trial comparing captopril (207 patients) with placebo (202 patients), whose purpose was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy to develop a model of medical treatment for patients before progression to ESRD. To model the course of illness after progression to ESRD and to extend the model to patients with NIDDM, we used data from the U.S. Renal Data System and published literature. Medical resource cost data were based predominantly upon Medicare reimbursement levels, published wholesale drug prices, and surveying health care providers. The economic model uses a payer perspective to estimate direct cost. The cost to society (indirect cost) associated with lost patient productivity due to ESRD was also estimated. Using this information, we predicted the costs incurred annually and over a lifetime if patients with IDDM and NIDDM and overt nephropathy were treated with either placebo or captopril. We also constructed a model of the overall prevalence of diabetic nephropathy to estimate the aggregate savings in total U.S. health care expenditures. RESULTS: Treatment with captopril resulted in an absolute direct cost savings or benefit of $32,550 per patient with IDDM over the course of a lifetime compared to treatment with placebo. For patients with NIDDM, the direct cost savings totaled $9,900 per patient. Absolute savings were found for indirect costs as well: $84,390 per patient with IDDM and $45,730 per patient with NIDDM. If captopril therapy were initiated in 1995 for patients with either IDDM or NIDDM and nephropathy, the aggregate health care cost savings (i.e. direct cost savings alone) would be $189 million a year for the year 1999 and $475 million a year in 2004, the present value of cumulative health care cost savings for these 10 years would be $2.4 billion. CONCLUSIONS: The use of captopril in diabetic nephropathy will provide significant savings in health care costs; in addition, it will result in savings in indirect cost, which reflects the broader societal benefit.

Economic aspects of treatment with captopril for patients with asymptomatic left ventricular dysfunction in The Netherlands.

OBJECTIVE: To estimate the costs and effects of preventive treatment with captopril compared with the current treatment policy in patients with asymptomatic left ventricular dysfunction after a myocardial infarction. METHODS: Estimates of effects are based on the results of the SAVE trial. Costs are estimated on the basis of current treatment patterns in four Dutch hospitals. All knowledge is incorporated in a mathematical model extrapolating the SAVE results to 20 years. RESULTS AND CONCLUSIONS: Captopril treatment is expected to increase survival at certain costs. The average additional costs per patient are estimated at DF1 2,491 in 4 years and at DF1 8,723 in 20 years of treatment. Costs per additional survivor after 4 years are estimated at DF1 69,126. After extrapolation of the results of the SAVE trial to 20 years, costs per life-year gained can be estimated at DF1 15,799. From univariate sensitivity analysis it appears that the results are highly sensitive for the costs of treatment with captopril and the occurrence and prevention of clinical heart failure. Varying all estimates randomly between upper and lower limits-in 5,000 simulations-an estimate of costs per life-year gained of DF1 15,729 is made for 20 years of treatment, with 95% of all estimates between DF10 and DF1 50, 000. On a national level, undiscounted costs are expected to increase up to approximately DF1 42 million annually during the first 40 years after introduction of the preventative strategy.

[Cost effectiveness of captopril after myocardial infarct; comment]. / Die Wirtschaftlichkeit von Captopril nach Myokardinfarkt.

BACKGROUND: In Germany approximately 88,000 people died as a result of acute myocardial infarction and approximately 300,000 people suffered from acute myocardial infarction in 1992. These data demonstrate the socioeconomic impact of coronary disease. In the SAVE-(Survival-and-Ventricular-Enlargement) study, Pfeffer et al. demonstrated a reduction of morbidity and mortality due to therapy with captopril in patients after myocardial infarction. In a retrospective, incremental cost-effectiveness-analysis, from the perspective of German statutory insurance fund, the economic impact of captopril after myocardial infarction has been analysed. PATIENTS AND METHOD: The basis for the economic evaluation has been the double-blind, placebo-controlled, clinical SAVE-study which included 2,231 patients having left ventricular dysfunction after acute myocardial infarction. Additional data e.g. average number of hospital days or average costs for hospitalisation per day was taken from published national statistical sources. In the cost-effectiveness-analysis, inputs (monetary units) and outputs (non-monetary units) were identified and measured. The cost-effectiveness (costs per life-year gained) demonstrates a relation between the costs of captopril-treatment, costs for myocardial infarction and costs for leftventricular insuffiency and the clinical benefit e.g. life years gained. RESULTS: Initially costs in the captopril-group are 3.7 Mio DM higher as in the placebo-group. But these costs are partly compensated by the cost reductions in the captopril-group, compared to the placebo-group (2,162,901 DM) the reduction of myocardial infarction and DM 556,518 cost reduction due to fewer patients with left ventricular dysfunction. The clinical benefit of the captopril treatment equals 495 life years gained. The cost-effectiveness-ratio is 2,000 DM cost for life year gained. CONCLUSION: The treatment with captopril after acute myocardial infarction is not only a clinically efficacious treatment, but also cost-effective in patients after acute myocardial infarction.